A positive association between RDW and coronary heart disease in the rheumatoid arthritis population: A cross-sectional study from NHANES

Previous research has indicated that higher red blood cell distribution width (RDW) increases the risk of coronary heart disease. However, no studies have established a link between RDW and coronary heart disease in the rheumatoid arthritis population. This research aims to explore the association between RDW and coronary heart disease among individuals with rheumatoid arthritis. We selected demographic data, laboratory data, lifestyle, and medical history from the National Health and Nutrition Examination Survey (NHANES), specifically including age, gender, poverty, RDW, race, BMI, diabetes, education, coronary heart disease, hypertension, cholesterol, smoking, and drinking. RDW and coronary heart disease were found to have a positive association in the rheumatoid arthritis population (OR = 1.145, 95%CI: 1.036–1.266, P = .0098), even after adjusting for factors such as age, gender, race, education level, smoking, and drinking. Subgroup analysis showed a stronger positive association, particularly in individuals aged 55–66 years, males, and the Hispanic White population with diabetes or hypercholesterolemia. There is a significant correlation between RDW and coronary heart disease among individuals with rheumatoid arthritis.


Introduction
Coronary heart disease (CHD) results from atherosclerotic plaque formation in coronary arteries, causing lumen stenosis and leading to cardiomyocyte ischemia.Plaque rupture exposes subendothelial collagen to blood, triggering platelet aggregation, coronary thrombosis, vascular occlusion, and cardiomyocyte necrosis.Recently, changing lifestyles have contributed to an increasing incidence of CHD, now recognized as one of the most common and serious diseases threatening human health worldwide and a leading cause of death. [1,2]DW, a routine blood test parameter calculated as the standard deviation of red cell volume divided by the mean cell volume, expressed as a percentage (RDW%), reflects the variability in red blood cell size.[3] Beyond hematological disorders, RDW is associated with various acute and chronic cardiovascular diseases, including coronary heart disease, heart failure, and atrial fibrillation.[4] RDW is implicated in chronic inflammation and is closely linked with patient mortality and the progression of cardiovascular events, serving as an independent predictor of outcomes and mortality in these events.[5][6][7][8] Rheumatoid arthritis (RA), a chronic systemic inflammatory disease, affects approximately 0.5% to 1.0% of the global population.Characterized by prolonged duration, involvement of multiple tissues, and a high disability rate, RA significantly impacts patient health.[9] Patients with RA experience disordered immune function and systemic vascular infiltration by inflammatory factors, resulting in an incidence of vascular events 1.5 to 2.0 times higher than the general population.[10] However, limited research exists on the relationship between increased RDW and the severity of coronary artery lesions in CAD patients with RA, including those with complications from RA.It remains unclear whether RDW is an independent risk factor for CHD in RA patients.This study aims to analyze the correlation of RDW with RA to investigate RDW diagnostic value in CHD patients with RA.

Population
This study utilized data from the National Health and Nutrition Examination Survey (NHANES) collected between 2011 and 2020. [11] total of 45,462 participants were involved in the NHANES survey over all 4 cycles.In our study, RDW values were missing for 8692 participants, CHD values for 13,111, and RA values for 22,423.Ultimately, our sample comprised 1236 individuals (Fig. 1).

Variables
RDW examination was conducted using a questionnaire.RDW tertiles were classified as low, middle, and high.RA diagnosis was based on reports from a physician or other healthcare professional.
Considered in this study were demographic data, laboratory data, lifestyle, and medical history. [12]Demographic data included age, gender, race, poverty, and education level.
Lifestyle factors covered smoking, drinking, and moderate recreational activities."Drinking" refers to regular alcohol consumption, and "smoking" to individuals who have smoked at least 100 cigarettes in their lifetime. [13]he study also included a history of diabetes, hypertension, and hypercholesterolemia. [14]

Statistical analysis
Data analysis was performed using a weighted approach.Both univariate and multivariate logistic regression were employed to assess the relationship between RDW and CHD.A general additive model and subgroup analysis were also utilized.R version 4.0.4 was used for all statistical analyses.A P value of .05 was deemed statistically significant.

Results
The total number of participants in this study was 1236 (Table 1).The mean age of the examined population was 61.107 years.Our findings indicate that factors such as age, gender, BMI, race, diabetes, hypertension, and hypercholesterolemia are strongly associated with the occurrence of CHD.However, poverty, education level, smoking, physical activity, and alcohol consumption were not significantly associated with CHD risk.

Univariate analysis
Table 2 presents the results of the univariate analysis.These results suggest that age, gender, race, RDW, BMI, diabetes, hypertension, and hypercholesterolemia are significantly related to the high incidence of CHD in the RA population (P < .05).

The association between RDW and CHD
Multivariate logistic regression was employed to assess the association between RDW and CHD in RA patients (Table 3).Our findings revealed that in Model 3, RDW was positively associated with CHD after adjusting for all confounding factors (OR = 1.187, 95%CI: 1.065-1.322,P = .0029).Additionally, we categorized RDW into 3 groups to further investigate its association with CHD.According to the fully adjusted model, an increase in RDW correlates with a higher incidence of CHD.

The linear relationship between RDW and CHD
A general additive model was used to illustrate the relationship between RDW and CHD in the RA population.Figure 2 shows an increased risk of CHD with higher RDW levels in RA patients.

Subgroup analysis
This section explores the relationship between RDW and CHD across various age groups, genders, races, and the presence of diabetes, hypertension, or hypercholesterolemia (Table 4).

Discussion
There is a significant association between RDW and the incidence of CHD in the RA population, indicating that higher RDW levels correlate with an increased risk of CHD.Subgroup analysis revealed a more pronounced association in males, Hispanic Whites, and individuals aged 56 to 66.
Rheumatoid arthritis is primarily characterized by synovitis and vasculitis, affecting multiple systems.Studies have highlighted that the cardiovascular system is one of the most frequently affected organs in RA patients, with cardiovascular events being the leading cause of mortality, [15] often linked to atherosclerotic disease.Subclinical coronary atherosclerosis [16] is common in RA patients.However, atherosclerosis is a systemic, chronic process where early detection and intervention are crucial for reducing the incidence and mortality of coronary heart disease in RA patients.
Inflammation serves as a common pathological basis for both RA and coronary atherosclerosis.Inflammatory factors are key pathogenic elements, [17] impacting vascular endothelium, liver, and other tissues.They increase blood viscosity, homocysteine (Hcy) levels, and insulin resistance, thereby promoting coronary atherosclerosis. [18]Consequently, RA presents a heightened risk for CHD.Given RA global prevalence, investigating CHD risk in RA patients is of significant practical importance.This research establishes an association between RDW and CHD in the RA population.Subgroup analysis identified high-sensitivity groups.A significant positive correlation between RDW and CHD was found in individuals aged 56 to 66.The association was strongest among RA men and Hispanic Whites.
However, this study has limitations.While it demonstrates an association between RDW and CHD, the cross-sectional design precludes definitive conclusions about causality.Additionally, despite including numerous confounding factors, some were not considered in our study.

Conclusion
A positive correlation exists between RDW and CHD in the RA population, with a stronger association observed in individuals aged 56-66, males, and the Hispanic White population, particularly those with diabetes or hypercholesterolemia.We adjusted all covariants in Table 1.95%CI = 95% confidence interval, BMI = body mass index, CHD = coronary heart disease, OR = odds ratio, RDW = red blood cell distribution.

Figure 1 .
Figure 1.Flow chart of subjects selection from the NHANES 2011 to 2020.NHANES = the National Health and Nutrition Examination Survey.

Figure 2 .
Figure 2. The linear relationship between red blood cell distribution width and coronary heart disease.

Table 1
Characteristics of participants in the study.

Table 2
Univariate logistic regression analysis of all variables with coronary heart disease among the rheumatoid arthritis population.

Table 3
Multiple logistic regression analysis of the relationship between red blood cell distribution width and coronary heart disease among the rheumatoid arthritis population.

Table 4
Subgroup analysis of the relationship between red blood cell distribution width and coronary heart disease among the rheumatoid arthritis population.